Abstract | BACKGROUND: METHODS: Whole blood samples from healthy volunteers were incubated in vitro in the presence and absence of pegnivacogin and platelet reactivity was analysed. In addition, platelet aggregometry was performed in blood samples from ACS patients in the RADAR trial featuring the intravenous administration of pegnivacogin as well as reversal by anivamersen. RESULTS: In vitro, pegnivacogin significantly reduced adenosine diphosphate-induced CD62P-expression (100% vs. 89.79±4.04%, p=0.027, n=9) and PAC-1 binding (100% vs. 83.02±4.08%, p=0.010, n=11). Platelet aggregation was reduced (97.71±5.30% vs. 66.53±9.92%, p=0.013, n=10) as evaluated by light transmission aggregometry. In the presence of the RNA-aptamer reversal agent anivamersen, neither CD62P-expression nor platelet aggregation was attenuated. In patients with ACS treated with aspirin and clopidogrel, residual platelet aggregation was significantly reduced 20 min after intravenous bolus of 1 mg/kg pegnivacogin (100% versus 43.21±8.23%, p=0.020). CONCLUSION: Inhibition of factor IXa by pegnivacogin decreases platelet activation and aggregation in vitro. This effect was negated by anivamersen. In ACS patients, platelet aggregation was significantly reduced after intravenous pegnivacogin. An aptamer-based anticoagulant inhibiting factor IXa therefore might be a promising antithrombotic strategy in ACS patients.
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Authors | Dawid L Staudacher, Vera Putz, Lukas Heger, Jochen Reinöhl, Marcus Hortmann, Steven L Zelenkofske, Richard C Becker, Christopher P Rusconi, Christoph Bode, Ingo Ahrens |
Journal | European heart journal. Acute cardiovascular care
(Eur Heart J Acute Cardiovasc Care)
Vol. 8
Issue 6
Pg. 520-526
(Sep 2019)
ISSN: 2048-8734 [Electronic] England |
PMID | 28403626
(Publication Type: Journal Article)
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Chemical References |
- Anticoagulants
- Aptamers, Nucleotide
- Oligonucleotides
- RB 006
- RB 007
- Factor IXa
- Thrombin
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Topics |
- Acute Coronary Syndrome
(mortality, therapy)
- Administration, Intravenous
- Anticoagulants
(therapeutic use)
- Aptamers, Nucleotide
(administration & dosage, pharmacology, therapeutic use)
- Case-Control Studies
- Factor IXa
(antagonists & inhibitors)
- Humans
- Oligonucleotides
(administration & dosage, pharmacology)
- Percutaneous Coronary Intervention
(methods)
- Platelet Aggregation
(drug effects)
- Thrombin
(pharmacology)
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